Drugs for Epilepsy

Question 1

4 components of Seizures

Answer 1

• are periods of neural hyper-excitation
• the forebrain begin to fire in massive synchronized bursts
• Blood flow to the brain is increased
• greater use of glucose & oxygen

Question 2

Prevalence of epilepsy

Answer 2

lifetime prevalence of about 4 %

Question 3

Epilepsy/ seizure disorder

Answer 3

the epilepsies are a group of neurological disorders characterised by spontaneous, recurrent seizures People with epilepsy have a low seizure threshold

Question 4

Causes of epilepsy

Answer 4

Genetic (70%)
Structural/ metabolic (30%)

Question 5

Common structural cases of epilepsy

Answer 5

brain scars, cancer/ benign tumor, vascular malformation

Question 6

Onset of Epilepsy

Answer 6

In many patients seizures begin in childhood, often before the age of 15 years.
Children with epilepsy will sometimes “outgrow” seizures or will have reduced frequency of seizures in adulthood.

Question 7

Comorbidities of epilepsy

Answer 7

• Cognitive – memory problems
• Psychiatric – anxiety, depression, ADHD, psychosis
• Also co-morbidities for asthma, migraine, stroke, ulcers

Question 8

Generalized Seizures

Answer 8

Occur throughout the cortex

Question 9

Partial Seizures

Answer 9

Occur in just one location of the cortex

Question 10

2 Types of Partial seizures

Answer 10

1. Simple partial
2. Complex Partial

Question 11

2 Types of Generalized seizures

Answer 11

1. Absence
2. Tonic Clonic

Question 12

Absence (petit mal) Seizures

Answer 12

• (do not usually cause lasting damage)
• Briefly unconscious, blank stare, no memory of attack (not aware that they had seizure)
• Lasts less than 30 seconds
• 3 per second spike and wave throughout whole brain

Question 13

Tonic Clonic (grand mal)

Answer 13

• occur less frequently than absence
• Unconscious, dramatic convulsions, no memory of attack
• Lasts less than 5 minutes
• Constant spiking throughout the whole brain

Question 14

status epilepticus

Answer 14

a seizure that lasts more than 5 mins

Question 15

Simple partial

Answer 15

• Conscious, memory of attack, sensory/motor/emotion symptoms
• Duration varies
• Localized spiking in neocortical or limbic area of brain

Question 16

Complex partial (temporal lobe)

Answer 16

• Conscious but non-responsive, automatisms, no memory of attack (temporal lobe)
• Duration varies
• Localized then spreading spiking in one or both temporal lobes
• Hippocampus is involved & patient has no memory of seizure

Question 17

Normal EEG Pattern

Answer 17

Low voltage, asynchronized

Question 18

EEG during absence seizure

Answer 18

Looks similar to delta wave pattern (these seizures are generated in the thalamus)

Question 19

EEG during tonic-clonic seizure

Answer 19

Asynchronous high voltage firing- period after seizure (brain recovering)- not a lot of firing

Question 20

Anti-seizure medications generally act by…

Answer 20

promoting GABA signaling or reducing the function of voltage gated ion channels

Question 21

Treatment for epilepsy

Answer 21

• A diet low in carbohydrates causes the body to metabolize fats into ketones (Ketogenic diet)

Question 22

Common side effects of anti-seizure medications

Answer 22

sleepiness, memory impairment, nausea/GI upset, dependence/withdrawal

Question 23

Consequences if Epilepsy is not managed

Answer 23

• Permanent brain damage
• Seizure worsening- death from seizures
• Difficulty learning
• breathing in food or saliva into the lungs during a seizure, which can cause aspiration pneumonia

Question 24

With excess amount of calcium

Answer 24

Neuron dies

Question 25

Phenobarbital (Luminal)

Answer 25

• a barbituate
• First drug for tonic-clonic and partial seizures
• Oldest drug still in use
• long half-life
• cheap

Question 26

Mechanism of Phenobarbital

Answer 26

enhances GABA-A system – keeps the GABA channel open longer – increases the inhibitory effect of GABA

Question 27

Phenytoin (Dilantin)

Answer 27

• Second drug for tonic-clonic and partial seizures
• less sedating than phenobarbital, also has long half-life
• Second oldest drug still in use

Question 28

Mechanism of Phenytoin

Answer 28

Blocks voltage dependent sodium channels (antagonist)
- Phenytoin blocks the channels and reduces the number of action potentials that a neuron can fire

Question 29

Ethosuximide (Zarontin)

Answer 29

The drug of choice for absence seizures

Question 30

Mechanism of Ethosuximide

Answer 30

Blocks voltage dependent calcium channels (antagonist)
- blocks one specific type of these calcium channels that is found in the thalamus and reduces the amount of glutamate neurotransmitter that is released in that brain region

Question 31

Carbamazepine (Tegretol)

Answer 31

• A treatment for tonic-clonic and partial seizures.
• also used to treat bipolar disorder

Question 32

Mechanism of Carbamazepine

Answer 32

Blocks voltage dependent sodium channels (antagonist)
- blocks the channels and reduces the number of action potentials that a neuron can fire. It has a mechanism of action similar to phenytoin but they have different side effects

Question 33

Valproate (Valproic acid) (Depakene)

Answer 33

• The first broad-spectrum drug – effective for absence, tonic-clonic, and partial seizures
• Used to treat bipolar disorder

Question 34

Mechanism of Valproate

Answer 34

Multiple and not fully understood.
- 1st MOA - Blocks voltage dependent sodium channels (antagonist). In this way it is similar to phenytoin and carbamazepine.
- 2nd MOA – opens up chromatin/DNA structure to allow more gene expression = epigenetics. One of genes that is expressed is for enzyme that makes GABA – more GABA = more inhibition of neuron firing

Question 35

GRIN1 Disorder/ Features of GRIN1 Encephalopathy

Answer 35

• Motor impairments – hypotonia, dystonia, hyperkinesis
• Cortical visual impairment (CVI) is reported for many patients
• Oculogyric crisis – abnormal eye movements – also associated with GLUT1 deficiency syndrome